P1170: CAR-T THERAPY IS EFFECTIVE AND SAFE IN TREATING RELAPSED/REFRACTORY LYMPHOMA WITH MALIGNANT SEROUS CAVITY EFFUSION
Authors: Lefu Huang, Peihua Lu
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated about 40%-50% of response rate in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma. Lymphoma with a high tumor burden may develop malignant effusion, which is associated with a very poor prognosis and cure options are limited. Patients with symptomatic pleural effusions were often excluded from CAR-T clinical trials, such as the ZUMA series. Aims: To explore the safety and efficacy of CAR-T therapy in R/R lymphoma with malignant serous cavity effusion, a phase I/II clinical trial was conducted (NCT05206071&NCT0491686 Methods: Eligible R/R aggressive lymphoma patients with serous cavity effusion confirmed by ultrasound, including pleural effusion, abdominal effusion, and pericardial effusion, were enrolled from July 2021 to December 2022. All patients received fludarabine 30 mg/m2/d and cyclophosphamide 250 mg/m2/d for 3 consecutive days (day−5 to day−3) followed by CAR-T cell infusion. PET-CT was performed on day 28 to evaluate the response rate. CAR-T cell proliferation in peripheral blood (PB) and effusion were detected by qPCR and flow cytometry (FCM). Results: Twenty-five patients with pre-CAR T effusions received CAR-T infusion with a median age of 46(8-72) years and a median of 3 (2-5) prior lines of therapies. Of 25 patients, 16 with diffuse large B-cell lymphoma (DLBCL) received CAR19/22 cocktail infusion consisting of 2×106/kg CAR19 and 5×105/kg CAR22. Nine patients with T-cell lymphoblastic lymphoma (T-LBL) received a dose of 1×106/kg CD7 CAR-T cells. Almost all patients had large mediastinal or abdominal masses, with a maximum diameter up to 18cm in the mediastinum. Twenty-two patients had genetic risk factors, such as TP53 mutation, double-hit, MYC, and TRA/D fusion genes. At the day 28 assessment, the best overall response rate (ORR) for DLBCL patients was 81.25% (13/16), including 56.25% (9/16) complete remission (CR) and 25% (4/16) partial remission (PR), The ORRs and CR rates for T-LBL patients can reach 77.78% (7/9) and 55.56% (5/9) respectively. In the 1-year evaluation, 43.75% (7/16) of DLBCL patients remained in CR. Within 2 months after CAR-T therapy, 55.56% (5/9) of T-LBL patients bridged into allogeneic hematopoietic stem cell transplantation, and 4 remained in CR, while 1 experienced non-relapse death. Fifteen patients with effusion volume overload were required indwelling catheters and their effusions were collected to quantitate CAR-T cells. By FCM, the median peak of CAR19 and CAR22 T cells in effusions were 5.66% (range: 0.21% - 72.29%) and 0.84% (range: 0% - 10.5%), respectively, occurred on day 15, while the median peak of CD7 CAR-T cells was 27.55% (range: 10.59% - 89.8%) on day 21. By qPCR, CAR19 cells persisted for beyond one year with durable remission (Pt.06, Fig.1). However, only low levels of CAR22 cells, even no genomic DNA replications were detected (Fig.1). All patients developed cytokine release syndrome (CRS), and 28% (7/25) experienced severe CRS (grade 3 or higher). Five patients developed neurotoxicity, including 2 with grade 3 neurotoxicity. Symptomatic treatment was effective in relieving toxicity. Summary/Conclusion: Our study demonstrated promising efficacy and safety of CAR-T therapy in R/R lymphoma with malignant effusion. Exciting proliferation of CAR-T cells in the effusions and also durable remissions were observed. However, more data on additional patients and longer observation time are needed. Figure 1Keywords: DLBCL, CD19, CAR-T, T cell lymphoma